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Diffuse optical tomography (DOT) has been investigated for diagnosing malignant breast lesions, but its accuracy relies on model-based image reconstructions, which in turn depends on the accuracy of breast shape acquisition. In this work, we have developed a dual-camera structured light imaging (SLI) breast shape acquisition system tailored for a mammography-like compression setting. Illumination pattern intensity is dynamically adjusted to account for skin tone differences, while thickness-informed pattern masking reduces artifacts due to specular reflections. This compact system is affixed to a rigid mount that can be installed into existing mammography or parallel-plate DOT systems without the need for camera-projector re-calibration. Our SLI system produces sub-millimeter resolution with a mean surface error of 0.26 mm. This breast shape acquisition system results in more accurate surface recovery, with an average 1.6-fold reduction in surface estimation errors over a reference method via contour extrusion. Such improvement translates to 25% to 50% reduction in mean squared error in the recovered absorption coefficient for a series of simulated tumors 1-2 cm below the skin.

OBJECTIVE Venous thromboembolism (VTE) can cause significant morbidity and mortality in hospitalized patients, and may disproportionately occur in patients with limited mobility following spinal trauma. The authors aimed to characterize the epidemiology and clinical predictors of VTE in pediatric patients following traumatic spinal injuries (TSIs). METHODS The authors conducted a retrospective cohort analysis of children who experienced TSI, including spinal fractures and spinal cord injuries, encoded within the National Trauma Data Bank from 2011 to 2014. RESULTS Of the 22,752 pediatric patients with TSI, 192 (0.8%) experienced VTE during initial hospitalization. Proportionally, more patients in the VTE group (77%) than in the non-VTE group (68%) presented following a motor vehicle accident. Patients developing VTE had greater odds of presenting with moderate (adjusted odds ratio [aOR] 2.6, 95% confidence interval [CI] 1.4–4.8) or severe Glasgow Coma Scale scores (aOR 4.3, 95% CI 3.0–6.1), epidural hematoma (aOR 2.8, 95% CI 1.4–5.7), and concomitant abdominal (aOR 2.4, 95% CI 1.8–3.3) and/or lower extremity (aOR 1.5, 95% CI 1.1–2.0) injuries. They also had greater odds of being obese (aOR 2.9, 95% CI 1.6–5.5). Neither cervical, thoracic, nor lumbar spine injuries were significantly associated with VTE. However, involvement of more than one spinal level was predictive of VTE (aOR 1.3, 95% CI 1.0–1.7). Spinal cord injury at any level was also significantly associated with developing VTE (aOR 2.5, 95% CI 1.8–3.5). Patients with VTE stayed in the hospital an adjusted average of 19 days longer than non-VTE patients. They also had greater odds of discharge to a rehabilitative facility or home with rehabilitative services (aOR 2.6, 95% CI 1.8–3.6). CONCLUSIONS VTE occurs in a low percentage of hospitalized pediatric patients with TSI. Injury severity is broadly associated with increased odds of developing VTE; specific risk factors include concomitant injuries such as cranial epidural hematoma, spinal cord injury, and lower extremity injury. Patients with VTE also require hospital-based and rehabilitative care at greater rates than other patients with TSI.

The purpose of this study was to evaluate adipose tissue distributions and hepatic and pancreatic fat contents using a 6-point Dixon MRI technique in type 2 diabetes mellitus (T2DM), and to assess associations between fat distributions and biochemical markers of insulin resistance. Intra-abdominal MRI was investigated in 14 T2DM patients, 13 age- and sex-matched healthy controls (HC) and 11 young HC using a 3 T Prisma MRI scanner. All T2DM subjects completed a fasting comprehensive metabolic panel, and demographic measurements were taken according to standardized methodologies. We observed excellent correlation (R2 = 0.94) between hepatic fat fraction quantified using 6-point Dixon MRI and gold standard MRS, establishing the accuracy and reliability of the Dixon technique. Significantly increased visceral adipose tissue (VAT) volumes were found in T2DM patients compared to age-matched HC (1569.81 ± 670.62 cm3 vs. 1106.60 ± 566.85 cm3, p = .04). We also observed a trend of increasing subcutaneous adipose tissues (SAT), and total abdominal fat (TAT) volumes in T2DM compared to age-matched HC. Hepatic fat fraction percentage (HFF%) was 44.6% higher in T2DM compared to age-matched HC and 64.4% higher compared to young HC. Pancreatic fat fractions in the head and body/tail were higher in T2DM patients compared to both healthy cohorts. We also observed correlations between fat contents of the liver and pancreas in T2DM patients, and association between biochemical markers of T2DM with HFF, indicating a risk for non-alcoholic fatty liver disease among T2DM. In summary, this study provides evidence of T2DM patients having increased liver and pancreatic fat, as well as increased adipose tissues.

OBJECTIVESports injuries present a considerable risk of debilitating spinal injury. Here, the authors sought to profile the epidemiology and clinical risk of traumatic spinal injuries (TSIs) in pediatric sports injuries.METHODSThe authors conducted a retrospective cohort analysis of pediatric patients who had experienced a sports-related TSI, including spinal fractures and spinal cord injuries, encoded in the National Trauma Data Bank in the period from 2011 to 2014.RESULTSIncluded in the analysis were 1723 cases of pediatric sports-related TSI, which represented 3.7% of all pediatric sports-related trauma. The majority of patients with TSI were male (81%), and the median age was 15 years (IQR 13–16 years). TSIs arose most often from cycling accidents (47%) and contact sports (28%). The most frequently fractured regions were the thoracic (30%) and cervical (27%) spine. Among patients with spinal cord involvement (SCI), the cervical spine was involved in 60% of cases.The average length of stay for TSIs was 2 days (IQR 1–5 days), and 32% of the patients required ICU-level care. Relative to other sports-related trauma, TSIs without SCI were associated with an increased adjusted mean length of stay by 1.8 days (95% CI 1.6–2.0 days), as well as the need for ICU-level care (adjusted odds ratio [aOR] 1.6, 95% CI 1.3–1.9). Also relative to other sports-related trauma, TSIs with SCI had an increased length of stay by 2.1 days (95% CI 1.8–2.6 days) and the need for ICU-level care (aOR 3.6, 95% CI 2.6–4.8).TSIs without SCI were associated with discharge to or with rehabilitative services (aOR 1.7, 95% CI 1.5–2.0), as were TSIs with SCI (aOR 4.0, 95% CI 3.2–4.9), both relative to other sports-related trauma. Among the patients with TSIs, predictors of the need for rehabilitation at discharge were having a laminectomy or fusion, concomitant lower-extremity injury, head injury, and thoracic injury. Although TSIs affected 4% of the study cohort, these injuries were present in 8% of patients discharged to or with rehabilitation services and in 17% of those who died in the hospital.CONCLUSIONSTraumatic sports-related spinal injuries cause significant morbidity in the pediatric population, especially if the spinal cord is involved. The majority of TSI cases arose from cycling and contact sports accidents, underscoring the need for improving education and safety in these activities.

Introduction: The delivery of mechanical thrombectomy in acute stroke can be challenging because it requires coordination between patient travel and multiple stroke team members across different locations in the hospital. A Real Time Location System (RTLS) can facilitate a streamlined workflow by determining a patient’s location, but the required infrastructure can be costly to set up. We investigated the feasibility of a machine learning based RTLS using an Internet Of Things (IOT) device prototype to coordinate acute stroke endovascular intervention. Methods: In this proof-of-concept study, study investigators programmed an IOT device to collect WiFi signals from different hospital zones relevant to the mechanical thrombectomy workflow. Different machine learning (ML) algorithms were trained on location labelled training WiFi signals to predict location. The accuracies of the different ML algorithms to predict unlabeled testing WiFi signals collected on a separate day were measured, in percentages. Results: The training and testing datasets contained 1,179 and 293 samples respectively, with 2,516 and 2,618 unique WiFi signals detected in each dataset. The trained neural network, random forest, support vector machine, K-nearest neighbors, decision tree and ensemble classifiers achieved accuracies of 96.6%, 96.2%, 97.3%, 97.3%, 83.6% and 97.3% on the testing dataset respectively. Additionally, the neural network model produced estimates of uncertainty, which were significantly associated with the correctness of predictions based on logistic regression analysis (p < 0.001). Conclusions: An IOT based real time location system with machine learning can accurately predict locations within the hospital, demonstrating immense potential for the future applications of streamlining delivery of acute stroke endovascular intervention.

Diffuse optical tomography (DOT) has emerged over the past few decades as a non-invasive imaging tool to quantitatively assess deep tissue's functional and anatomical information. It has seen widespread use in various preclinical and clinical research fields, leading to a cumulative understanding of the technique and its potential applications. Over the years, the field of diffuse optics has encountered increasingly complex limitations, including ill-posedness, processing time, limited optodes density, etc., giving rise to novel and more sophisticated developments on the theoretical, algorithmic, computational, and instrumentation levels. In this chapter, we aim to present the theoretical basis of near-infrared diffuse optical tomography and diffuse correlation tomography. We introduce the state-of-the-art in computational and algorithmic perspectives, which seeks to improve the spatial resolution of reconstructed images while concurrently reducing the computational burden of solving high-dimensional inverse problems. We conclude by providing a survey of the most relevant applications of DOT currently undergoing clinical testing.

e15017 Background: Platelets play significant roles in inflammation, immune regulation, and intracellular communication processes involved in tumor pathogenesis. Aberrant platelet activation has been associated with tumor progression and metastasis, however, cancer patient platelet deep profiling remains underutilized. New tools are needed for rapid high throughput quantification of potential altered platelet secretome in cancer patients. Such technology may provide novel insights into impactful cancer-associated biomarkers. Methods: We have developed a high throughput multiplexed proteomic technology to profile platelet cytokine content and releasates and performed a pilot study in healthy patients versus triple negative breast cancer (TNBC). Macrochambers of the CodePlex chip were pre-patterned with a 23-plex antibody IsoPlexis Human Adaptive Immune Panel: GM-CSF, Granzyme B, IFN-g, IL-10, IL-13, IL-15, IL-17A, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IP-10, MCP-1, MIP-1a, MIP-1b, perforin, sCD137, TGF-b1, TNF-a, TNF-b. 2% BSA/PBS was used as background control. The chips are loaded into an IsoLight automation system, releasates measured by fluorescence ELISA, and analysis performed by IsoSpeak software. In a pilot study to test feasibility, platelets were meticulously harvested from triple negative breast cancer patients (n=2) and healthy controls (n=2) and stimulated for 30 minutes (ADP or TRAP-6) to promote cytokine release. Both the supernatants and platelet lysates were then loaded on CodePlex chips and analyzed. Results: The methodology of bulk proteomic measurements has previously been validated in a variety of biofluids such as serum/plasma, cerebrospinal fluid, tracheal washes, and cell culture supernatants. Freshly isolated platelets activated by TRAP6 generally released more cytokines than those activated by ADP stimulation in both healthy controls and disease samples. Interestingly, platelet releasates in supernatants from TNBC patients demonstrated increased pro-tumor IL-8 and IL-9, and reduced antitumor IFN-g compared to healthy controls. Higher levels of IL-8 and IL-9 and minimal IFN-g were detected at similar activation concentrations, in platelet lysates from both healthy and TNBC platelets. This suggests that TNBC may alter platelet content and/or activation. Increased numbers are being performed to validate these initial results. Conclusions: From this small pilot study, multiplexing quantitative proteomic analysis is potentially useful in detecting differential cytokine profile in platelet releasates and lysate contents between TNBC patients and healthy controls. Quantifying the platelet proteomes in cancer patients using high throughput proteomics may provide valuable insights to dissect cancer-platelet crosstalk and potential pathogenesis mechanisms.

INTRODUCTION: Surgical outcomes and healthcare utilization have been shown to vary based on patient insurance status. We analyzed whether patients’ insurance affects case urgency for and readmission after craniotomy for meningioma resection, using benign meningioma as a model system to minimize confounding from the disease-related characteristics of other neurosurgical pathologies. METHODS: We analyzed 90-day readmission for patients who underwent resection of a benign meningioma in the Nationwide Readmission Database from 2014–2015. RESULTS: A total of 9783 meningioma patients with private insurance (46%), Medicare (39%), Medicaid (10%), self-pay (2%), or another scheme (3%) were analyzed. 72% of all cases were elective; with 78% of cases in privately insured patients being elective compared to 71% of Medicare (p>0.05), 59% of Medicaid patients (OR 2.3, p

Background. Although immunotherapy has led to exceptional and durable clinical response, the majority of patients respond poorly to the current immunotherapies. Growing evidence has linked some of the poor responsiveness to the gut microbiota, and the modulation of gut microbiome composition is becoming a promising new strategy to enhance immune checkpoint inhibitor (ICI) treatment outcome. Mouse tumor modelling under germ-free (GF) conditions combined with introduction of defined bacterial strains could be a useful approach to investigate the impact of microbiota on ICI efficacy, as well as understanding the underlying mechanisms. We previously demonstrated that GF mice exhibited a significantly poor response to anti-PD-1 therapy when compared to the specific pathogen free (SPF) mice in a subcutaneous MC38 colorectal cancer model, which is consistent with other reports. Methods. Introduction of a single strain of Bacillus in the GF-environment was assessed for its impact on the anti-mouse PD-1 monoclonal antibody (mAb) therapy in GF-mice and SPF mice, both for efficacy and pharmacodynamics tumor infiltrating lymphocytes (TILs) profiling. C57BL/6 mice were inoculated subcutaneously with MC38 tumor cells and when the tumors were reached 80-120mm3, the mice were randomized for isotype or anti-PD-1 mAb treatment. Fecal sample 16S rRNA analysis (NGS) was used to confirm the gut bacteria status. Results. The MC38 tumor in GF mice has significantly fast baseline growth kinetics, even with the introduction of Bacillus under GF conditions compared to SPF mice, suggesting tumor immunity was not enhanced by Bacillus. Despite the introduction of Bacillus, GF mice also showed reduced response to anti-PD-1 treatment when compared to the SPF mice as previously reported, further confirming that introduction of Bacillus had minimal effects on the efficacy of anti-PD-1 therapy. Moreover, the SPF mice and GF mice with Bacillus exhibited distinct profiles of TILs, consistent with distinct efficacies as observed. GF free mice showed a lower frequency of CD45+ TILs in comparison to SPF mice. In addition, GF mice exhibited lower frequency of CD8+ TILs and TIL- NKT when compared to the SPF mice, both of which are consistent with the stronger efficacy seen in SPF mice. Meanwhile, GF mice also exhibited higher granulocytic myeloid derived suppressor cells (gMDSC) and lower M1/M2 ratio, both of which imply a more suppressive tumor microenvironment in GF mice. Fecal sample analysis using 16S rRNA analysis confirmed a single strain of Bacillus was indeed introduced into the guts of all the GF mice. Conclusions. The GF conditions provide a useful environment for the investigation of specific microbiota strains on the impact on ICI treatment outcome. In summary, the introduction of Bacillus in GF mice did not impact the efficacy of anti-PD-1, thus suggesting that other strain(s) of gut microbiota in SPF mice may impact this and need to be investigated. Citation Format: Tao Yang, Bonnie Xiaobo Chen, Rongfei Lu, Xiaoyu An, Mingfa Zang, Jingjun Li, Sheng Guo, Wubin Qian, Jian Fei, Tongyang Hao, Edward Xu, Henry Li. The introduction of a single strain of Bacillus into a germ-free environment did not impact the anti-PD-1 efficacy in a MC38 syngeneic model [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2021 Oct 7-10. Philadelphia (PA): AACR; Mol Cancer Ther 2021;20(12 Suppl):Abstract nr P103.

Malignant breast lesions manifest in a variety of shapes and configurations. Here we propose an algorithm utilizing anisotropic-tumor-prior guided diffuse optical tomography (DOT) reconstructions to recover an unknown tumor’s orientation and shape anisotropy.

Obesity-related conditions including heart disease, stroke, and type 2 diabetes are leading causes of preventable death. Recent evidence suggests that altered myocellular lipid metabolism in obesity may lead to increased insulin resistance (IR) that predisposes to these disorders. To test the hypothesis that muscles rich in type I vs. type II muscle fibers would exhibit similar changes in intramyocellular lipid (IMCL) and extramyocellular lipid (EMCL) content in obesity, we utilized a new four-dimensional multi echo echo-planar correlated spectroscopic imaging technique that allows separate determination of IMCL and EMCL content in individual calf muscles in obese vs. normal healthy human subjects. Calf muscles were scanned in 32 obese and 11 healthy subjects using a 3T MRI/MRS scanner, and IR in the obese subjects was documented by glucose tolerance testing. In obese subjects, elevation of both IMCL and EMCL content was observed in the gastrocnemius and tibialis anterior muscles (with mixed type I and II fiber content), while a significant increase in only IMCL content (+48%, p

This paper presents coupled transient thermal and electromagnetic finite element analysis of quench in the Q2, Q3, and dipole superconducting magnets using Vector Fields Quench code. Detailed temperature distribution within coils and aluminum force collars were computed at each time step. Both normal (quench with dump resistor) and worst-case (quench without dump resistor) scenarios were simulated to investigate the maximum temperatures. Two simulation methods were utilized, and their algorithms, implementation, advantages, and disadvantages are discussed. The first method simulated the coil using nonlinear transient thermal analysis directly linked with the transient circuit analysis. It was faster because only the coil was meshed and no eddy current was modeled. The second method simulated the whole magnet including the coil, the force collar, and the iron yoke. It coupled thermal analysis with transient electromagnetic field analysis which modeled electromagnetic fields including eddy currents within the force collar. Since eddy currents and temperature in the force collars were calculated in various configurations, segmentation of the force collars was optimized under the condition of fast discharge.

An AlGaN/GaN high-electron-mobility transistor (HEMT) with a novel source-connected air-bridge field plate (AFP) is proposed. The device features a metal field plate (FP) that jumps from the source over the gate region and lands between the gate and drain. The fabrication process is based on a commercially available radio-frequency GaN-on-SiC technology. Device characteristics for this work were optimized via layout changes only. When compared to a similar-sized HEMT device with a conventional FP structure, the AFP not only minimizes the parasitic gate-to-source capacitance but also exhibits a higher off-state breakdown voltage and one order of magnitude lower drain leakage current. In a device with a gate-to-drain distance of 6 μm and a gate length of 0.8 μm, a three-times-higher forward blocking voltage of 375 V was obtained at VGS = -5 V. In contrast, a similar-sized HEMT with a conventional FP can only achieve a breakdown voltage no higher than 125 V using this process, regardless of device dimensions. The specific on-resistance for the device with the proposed AFP is 0.58 mΩ·cm2 at VGS = 0 V, which compares favorably with 0.79 mΩ·cm2 for the best device with a conventional FP.

The purpose of the present study was to compare the effects of alendronate (ALN) and alfacalcidol (ALF) on the femoral bone mass and bone strength in orchidectomized rats and to clarify the skeletal benefits of combined administration of ALN and ALF. Fifty male Sprague-Dawley rats, 3 months of age, were randomized by the stratified weight method into five groups: the age-matched control (CON), orchidectomy (ORX), ORX + ALN (2.5 microg/kg, s.c., 5 times a week), ORX + ALF (0.1 microg/kg, p.o., 5 times a week), and ORX + ALN + ALF groups. After 12 weeks of feeding, the femoral distal metaphysis and mid-diaphysis were processed for peripheral quantitative tomographic analysis and biomechanical testing. In the femoral distal metaphysis, ALN prevented the ORX-induced reduction in the trabecular volumetric bone mineral density (vBMD) and breaking energy, and ALF prevented the ORX-induced reduction in the trabecular vBMD and increased the breaking energy to values above those observed in the CON group. Both ALN and ALF increased the maximum load to values above those observed in the ORX group. The improvements in parameters described above were more pronounced when ALN and ALF were administered in combination. In the femoral mid-diaphysis, on the other hand, ALN did not significantly affect the cortical bone parameters, whereas ALF increased the cortical area and maximum load to values above those observed in the ORX group. Furthermore, no apparent benefit of combined administration of ALN and ALF was observed. These findings suggest differential effects of ALN and ALF on femoral bone mass and the beneficial effects of combined administration of ALN and ALF on the trabecular bone of the femur in ORX rats.

In this paper, a floating RESURF EDMOS (BV = 55 V, Ron,sp = 36.5 mOmegamiddotmm2) with 45% increased ruggedness and 400% enhanced safe operating area (SOA) is discussed and compared to the conventional EDMOS structure. The proposed EDMOS has both drain and source engineering to enhance device ruggedness, not only via reducing the base resistance of the parasitic bipolar transistor, but also suppressing the base current of the parasitic bipolar transistor at high VGS and high VDS situations, which will also improve the device SOA. Furthermore, the buried deep Nwell allow the device to have better tradeoff between breakdown voltage and on-resistance.

A reduced surface electric field in an AlGaN/GaN high electron mobility transistor (HEMT) is investigated by employing a localized Mg-doped layer under the two-dimensional electron gas (2-DEG) channel as an electric field shaping layer. The electric field strength around the gate edge is effectively relieved and the surface electric field is distributed evenly as compared with those of HEMTs with conventional source-connected field plate and double field plate structures with the same device physical dimensions. Compared with the HEMTs with conventional source-connected field plates and double field plates, the HEMT with a Mg-doped layer also shows that the breakdown location shifts from the surface of the gate edge to the bulk Mg-doped layer edge. By optimizing both the length of Mg-doped layer, Lm, and the doping concentration, a 5.5 times and 3 times the reduction in the peak electric field near the drain side gate edge is observed as compared with those of the HEMTs with source-connected field plate structure and double field plate structure, respectively. In a device with VGS = −5 V, Lm = 1.5 μm, a peak Mg doping concentration of 8×1017 cm−3 and a drift region length of 10 μm, the breakdown voltage is observed to increase from 560 V in a conventional device without field plate structure to over 900 V without any area overhead penalty.